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First-in-human phase I study of ABBV-838, an antibody-drug conjugate targeting SLAMF7/CS1 in patients with relapsed and refractory multiple myeloma

Purpose: ABBV-838 is an antibody-drug conjugate targeting a unique epitope of CD2 subset 1, a cell-surface glycoprotein expressed on multiple myeloma cells. This phase I/Ib first-in-human, dose-escalation study (trial registration ID: NCT02462525) evaluated the safety, pharmacokinetics, and prelimin...

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Bibliographic Details
Main Authors: Vij, Ravi (Author) , Raab, Marc-Steffen (Author)
Format: Article (Journal)
Language:English
Published: May 2020
In: Clinical cancer research
Year: 2020, Volume: 26, Issue: 10, Pages: 2308-2317
ISSN:1557-3265
DOI:10.1158/1078-0432.CCR-19-1431
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1158/1078-0432.CCR-19-1431
Verlag, lizenzpflichtig, Volltext: https://clincancerres.aacrjournals.org/content/26/10/2308
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Author Notes:Ravi Vij, Rajneesh Nath, Daniel E.H. Afar, María-Victoria Mateos, Jesús G. Berdeja, Marc S. Raab, Andreas Guenther, Joaquín Martínez-López, Andrzej J. Jakubowiak, Xavier Leleu, Katja Weisel, Shekman Wong, Scott Gulbranson, James P. Sheridan, Anita Reddy, Bruno Paiva, Anil Singhal, Jesús F. San-Miguel, and Philippe Moreau
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Summary:Purpose: ABBV-838 is an antibody-drug conjugate targeting a unique epitope of CD2 subset 1, a cell-surface glycoprotein expressed on multiple myeloma cells. This phase I/Ib first-in-human, dose-escalation study (trial registration ID: NCT02462525) evaluated the safety, pharmacokinetics, and preliminary activity of ABBV-838 in patients with relapsed and refractory multiple myeloma (RRMM). - Patients and Methods: Eligible patients (≥18 years) received ABBV-838 (3+3 design) intravenously starting from 0.6 mg/kg up to 6.0 mg/kg for 3-week dosing intervals (Q3W). Patients could continue ABBV-838 for up to 24 months. Assessment of alternate dosing intervals (Q1W and Q2W) was conducted in parallel. - Results: As of March 2017, 75 patients received at least one dose of ABBV-838. The most common any-grade treatment-emergent adverse events (TEAE) were neutropenia and anemia (28.0% each), fatigue (26.7%), and nausea (25.3%). Grade 3/4/5 TEAEs were reported in 73.3% of patients across all treatment groups; most common were neutropenia (20.0%), anemia (18.7%), and leukopenia (13.3%). Grade 3/4/5 ABBV-838-related TEAEs were reported by 40.0% of patients across all treatment groups. Overall, 4.0% of patients experienced TEAEs leading to death, none ABBV-838 related. The MTD was not reached; the selected recommended dose for the expansion cohort was 5.0 mg/kg Q3W. Pharmacokinetic analysis showed that exposure was approximately dose proportional. The overall response rate was 10.7%; very good partial responses and partial responses were achieved by 2 (2.7%) and 6 (8.0%) patients, respectively. - Conclusions: These results demonstrate that ABBV-838 is safe and well-tolerated in patients with RRMM with a very limited efficacy.
Item Description:Gesehen am 23.09.2020
Physical Description:Online Resource
ISSN:1557-3265
DOI:10.1158/1078-0432.CCR-19-1431

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